M-4312-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

Variant has been reported in ClinVar as Benign (★).

Frequency

Mitomap GenBank:
𝑓 0.028 ( AC: 1683 )

Consequence

TRNI
missense

Scores

Mitotip
Benign
3.5

Clinical Significance

Benign criteria provided, single submitter B:1
No linked disesase in Mitomap

Conservation

PhyloP100: 2.50
Variant links:
Genes affected
TRNI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)
ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]
TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)
ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]
TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant M-4312-C-T is Benign according to our data. Variant chrM-4312-C-T is described in ClinVar as [Benign]. Clinvar id is 689877.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
High frequency in mitomap database: 0.0275

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRNIunassigned_transcript_4790 c.50C>T p.Ala17Val missense_variant Exon 1 of 1
ND2unassigned_transcript_4793 c.-158C>T upstream_gene_variant
TRNMunassigned_transcript_4792 c.-90C>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt

Frequencies

GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
0.028
AC:
1683
Gnomad homoplasmic
AF:
0.012
AC:
663
AN:
56418
Gnomad heteroplasmic
AF:
0.000035
AC:
2
AN:
56418
Alfa
AF:
0.00173
Hom.:
68

Mitomap

No disease associated.

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

MELAS syndrome Benign:1
Jul 12, 2019
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The NC_012920.1:m.4312C>T variant in MT-TI gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Mitotip
Benign
3.5
Hmtvar
Benign
0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs193303033; hg19: chrM-4313; API